EFFECT OF METALS ON INTERLEUKIN-6 (IL-6) MITOGENIC STIMULATION OF MURINE HYBRIDOMA CELLS

The effect of several divalent metal cations (Co, Cu, Zn, Hg and Pb) on the proliferative response of B9 hybridoma cells to IL-6 has been investigated. At concentrations which are not cytotoxic all the metals inhibited proliferation. The inhibition by Cd and Pb was dependent on both time of addition of the metal and IL-6 concentration. Cd (10 muM) and Pb (50 muM) added at the same time as IL-6 were inhibitory but added 24h later had no effect. Increasing the concentration of IL-6 overcame the inhibitory effect of Cd (10 muM) and Pb (50 muM). Inhibition caused by the other metals was independent of either time of addition or IL-6 concentration. IL-6 did not stimulate an increased intracellular concentration of metallothionein suggesting that the protective effect of IL-6 is not mediated via induction of metallothionein. The results suggest that there are at least two distinct metal sensitive events in B9 proliferation, i) IL-6 reversible inhibition by Cd and Pb ii) IL-6 independent inhibition by Co, Cu and Hg.